Distinct monkeypox virus lineages co-circulating in humans before 2022

Nnaemeka Ndodo, Jonathan Ashcroft, Kuiama Lewandowski, Adesola Yinka-Ogunleye, Chimaobi Chukwu, Adama Ahmad, David King, Afolabi Akinpelu, Carlos Maluquer de Motes, Paolo Ribeca, Rebecca P Sumner, Andrew Rambaut, Michael Chester, Tom Maishman, Oluwafemi Bamidele, Nwando Mba, Olajumoke Babatunde, Olusola Aruna, Steven T Pullan, Benedict GannonColin S. Brown, Chikwe Ihekweazu, Ifedayo Adetifa, David O. Ulaeto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The 2022 global mpox outbreak raises questions about how this zoonotic disease established effective human-to-human transmission and its potential for further adaptation. The 2022 outbreak virus is related to an ongoing outbreak in Nigeria originally reported in 2017, but the evolutionary path linking the two remains unclear due to a lack of genomic data between 2018, when virus exportations from Nigeria were first recorded, and 2022, when the global mpox outbreak began. Here, 18 viral genomes obtained from patients across southern Nigeria in 2019-2020 reveal multiple lineages of monkeypox virus (MPXV) co-circulated in humans for several years before 2022, with progressive accumulation of mutations consistent with APOBEC3 activity over time. We identify Nigerian A.2 lineage isolates, confirming the lineage that has been multiply exported to North America independently of the 2022 outbreak originated in Nigeria, and that it has persisted by human-to-human transmission in Nigeria for more than 2 years before its latest exportation. Finally, we identify a lineage-defining APOBEC3-style mutation in all A.2 isolates that disrupts gene A46R, encoding a viral innate immune modulator. Collectively, our data demonstrate MPXV capacity for sustained diversification within humans, including mutations that may be consistent with established mechanisms of poxvirus adaptation.

Original languageEnglish
Pages (from-to)2317-2324
Number of pages10
JournalNature Medicine
Issue number9
Early online date14 Sept 2023
Publication statusPublished - 14 Sept 2023


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